The design, development and application of a dual-beam spectral-domain optical coherence tomography system for the non-invasive assessment of vascular dynamics by statistical means

Abstract:

This assertion underscores the importance of haematological dynamic assessment, which can benefit greatly from non-invasive high-resolution imaging of blood flow especially at the microvascular level. This importance is further highlighted in oncological applications with recent emphasis on tumour vasculature, angiogenic processes and developments of anti-angiogenic therapies.
Optical coherence tomography (OCT) has established itself a firm foothold in the realm of non-invasive optical medical diagnostic imaging, enabling in vivo cross-sectional tomographic visualisation of the internal microstructure of biological systems, and is now considered an optical analogue to CT or MRI, but with microscopic resolution. The original concept of OCT was to enable non-invasive real time in situ imaging of tissue microstructure with a resolution approaching that of histology, but without the need for tissue excision and processing; i.e. an optical biopsy. Doppler OCT has been the predominant force for the quantification of moving particles within media. However, despite the advancements of DOCT techniques, phase shift assessment of velocity values requires that the angle between the incident light source and the vessel in question be known a priori. Due to the extensive tortuosity of the microvasculature, the Doppler angular dependency may lead to incomplete vascular maps in vivo. In an effort to surmount the restrictions imposed by angular uncertainties, the in-house cross-correlation dual-beam SdOCT (db-SdOCT) system presented here operates by quasi-simultaneous illumination and measurement of two distinct planes; this forms a miniature time-gate. By analysis of light intensity fluctuations at two points a known distance apart, transit times may be deduced via temporal cross-correlation, thereby yielding velocity values irrespective of vessel tortuosity. This technique eliminates the need for phase sensitive detection and instead utilises the temporally evolving phase itself as a metric for quantifying velocity by statistical means.
Cross-correlation db-SdOCT analysis creates a variable velocity measurement range and can be set based on the flexibility of its parameters i.e. acquisition and beam separation distance. In general, the preliminary in vitro results obtained indicated a tentative first step in developing a robust tool for flow velocity quantification by means of cross-correlation. However, in order to investigate the applicability of the method for in vivo studies, a full characterisation of the system was performed and is outlined in terms of beam separation, functional extensions (axial profiling, discerning flow direction, turbulence investigations and pulsatility studies), and optimisation of the optics involved. Endoscopic OCT offers a means of obtaining high-resolution and high-speed depth-resolved visualisation of deep tissue structures in vivo. With a view to future potential applications of the db-SdOCT system and algorithm for intravital exploratory applications, a macro-model of a side-view endoscopic device was constructed to investigate the efficacy of this simplified approach. The capabilities of in vivo assessment were examined in the analysis of the nailfold plexus. The resulting velocity, directionality and axial profiling computation of the constituent capillaries have shown the capability of the db-SdOCT method in such environments.
This work chronicles the design, development and implementation of a db-SdOCT system for velocity assessment by cross-correlation analysis and its outlined functional extensions provide a multi-faceted modality for in vivo research. Adaptation of this method into existing OCT regimes is straightforward and cost-effective, providing a means of dynamic assessment, free from angularly induced artifacts.